2-132918641-A-G

Variant names:

• chr2-132918641-A-G
• rs1036543
• NM_207363.3:c.580-39725T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207363.3(NCKAP5):​c.580-39725T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,094 control chromosomes in the GnomAD database, including 8,944 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (8944 hom., cov: 32)
• Consequence: NCKAP5 NM_207363.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600
• Publications: 8 publications found

Genes affected

NCKAP5 (HGNC:29847): (NCK associated protein 5) Predicted to be involved in microtubule bundle formation and microtubule depolymerization. Predicted to be active in microtubule plus-end. [provided by Alliance of Genome Resources, Apr 2022]

NCKAP5-AS1 (HGNC:41246): (NCKAP5 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCKAP5	NM_207363.3	c.580-39725T>C		intron_variant	Intron 8 of 19	ENST00000409261.6	NP_997246.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCKAP5	ENST00000409261.6	c.580-39725T>C		intron_variant	Intron 8 of 19	5	NM_207363.3	ENSP00000387128.1
NCKAP5-AS1	ENST00000424510.1	n.95+2990A>G		intron_variant	Intron 1 of 1	1
NCKAP5	ENST00000409213.5	c.580-39725T>C		intron_variant	Intron 8 of 17	5		ENSP00000386952.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36108 AN: 151976 Hom.: 8900 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.0989

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.0532

Gnomad FIN AF: 0.0820

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0350

Gnomad OTH AF: 0.221

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.238 AC: 36205 AN: 152094 Hom.: 8944 Cov.: 32 AF XY: 0.239 AC XY: 17743 AN XY: 74362

African (AFR) AF: 0.586 AC: 24279 AN: 41440

American (AMR) AF: 0.338 AC: 5149 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0989 AC: 343 AN: 3468

East Asian (EAS) AF: 0.467 AC: 2415 AN: 5174

South Asian (SAS) AF: 0.0522 AC: 252 AN: 4826

European-Finnish (FIN) AF: 0.0820 AC: 869 AN: 10604

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0350 AC: 2381 AN: 68012

Other (OTH) AF: 0.219 AC: 463 AN: 2110

Alfa AF: 0.137 Hom.: 8040

Bravo AF: 0.282

Asia WGS AF: 0.270 AC: 936 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.65
PhyloP100		0.0060
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1036543; hg19: chr2-133676214;